Patent GB-1462421-A (GB)
Title: 6-a-amidino-and -'midoylaminoalkanoylamino aracylamino-penicillanic acids and their preparation
IPC: A61P31/04
Filed: 1974-01-14
Abstract: 1462421 Penicillin-derived amidines PFIZER Inc 14 Jan 1974 [14 Dec 1973] 01673/74 Addition to 1418656 Heading C2C The invention comprises (with certain exceptions having the effect of excluding compounds claimed in the parent Specification) compounds of formula and their pharmaceutically acceptable salts, wherein Ar is Ph, p-HOC 6 H 4 , or 2- or 3-thienyl; Z is V-A-CO-; A is CH 2 , CH 2 CH 2  or C 2-4  alkylidene; V is (R 2 )N : C(R 5 )N(R 1 )-, HN: C(R 6 )NH- or (R 11 )(R 12 )C(OH)C(:NH)NH-; R 1  and R 2  are each hydrogen or alkyl containing from 1 to 3 carbon atoms; R 5  is naphthyl; phenyl; benzyl; monosubstituted phenyl wherein said substituent is fluoro, chloro, iodo, bromo, methyl, methoxy, acetyl, dimethylamino, amidino, phenyl, cyano, trifluoromethyl, amino, hydroxy, alkanoylamino containing from 2 to 5 carbon atoms, methylthio, nitro, carbethoxy, carboxamido, methylsulphonyl, sulphamoyl, N-methylsulphamoyl or N,N-dimethylsulphamoyl; disubstituted phenyl, wherein each substituent is hydroxy, alkoxy containing from 1 to 5 carbon atoms, methylthio, acetoxy, methylsulphonyl, trifluoromethyl, N,N-dimethylsulphamoyl, iodo, chloro, fluoro, bromo, cyano, carbethoxy or allyloxy; trisubstituted phenyl, wherein each substituent is fluoro, chloro, bromo, iodo or methoxy; or substituted benzyl wherein said substituent is chloro, fluoro, methoxy, hydroxy, dichloro, methyl or trifluoromethyl; R 6  is a first sub-group consisting of furyl; di-bromo-2-furyl; thienyl, thenyl; thiazolyl; 2-benzoxazolyl; 2-benzo-γ-pyronyl; 2- benzothiazolyl; 2-benzothienyl; substituted 2- benzothienyl wherein said substituent is fluoro, chloro or bromo; isothiazolyl; oxazolyl; isoxazolyl; 1,2,3-thiadiazolyl; 2,3-dihydro-1,4-thiazinyl; benzofuryl; mono- and di-substituted thienyl wherein said substituent is bromo, chloro, methoxy, methyl, sulphamoyl of the formula R 7 R 8 NSO 2 - wherein R 7  and R 8  are each hydrogen or alkyl containing from 1 to 3 carbon atoms; or monomethyl substituted thiazolyl, isothiazolyl, oxazolyl or isoxazolyl; a second sub-group, R 9 , wherein R 9  is pyridyl; pyrimidinyl; pyridazinyl, pyrazinyl; benzimidazolyl; pyrryl; 2-pyrrolinyl; picolyl; substituted pyridyl wherein said substituent is fluoro, chloro, bromo or 2,6-dichloro; imidazo- [1,2-a]pyridyl, quinoxalinyl, quinolyl, isoquinolyl, imidazolyl or pyridyl-1-oxide; a third subgroup, R 10 CH 2 -, wherein R 10  is alkylthio containing from 1 to 3 carbon atoms; alkylsulphinyl containing from 1 to 3 carbon atoms; alkylsulphonyl containing from 1 to 3 carbon atoms; phenylthio; benzylthio; substituted phenylthio wherein said substituent is methyl, methoxy, fluoro, chloro or bromo; alkoxy containing from 1 to 3 carbon atoms; phenoxy; substituted phenoxy wherein said substituent is chloro, 3,5-dichloro and 3,4-dichloro; fluoro; chloro; hydroxy; amino; or substituted amino wherein said substituent is alkanoyl containing from 2 to 4 carbon atoms, alkyl containing from 1 to 3 carbon atoms, benzoyl, benzenesulphonyl, substituted benzoyl wherein said substituent is 3,4-dichloro and chloro, 2-thenoyl, phenyl or substituted phenyl wherein said substituent is 3,4-dichloro or chloro; R 11  is hydrogen or alkyl containing from 1 to 3 carbon atoms; and R 12  is phenyl or alkyl containing from 1 to 3 carbon atoms. These compounds are prepared by reacting a corresponding penicillin (A) in which Z is (R 1 )NH-A-CO-, with the appropriate iminoether or -thioether. Both (I) [Z=NH 2 CH 2 C(iNH)- NH-A-CO] and (A) may be prepared by hydrogenolysing their N-benzyloxycarbonyl analogues. Antibacterial compositions which may be administered orally, parenterally or topically comprise compounds of the above Formula (I).